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Global riactice Leader's in Brain Science

9/12 (Wed) 15:00 Special Seminar
Name : 관리자 | Date : 2018.09.10 11:49 | Views : 1111

Title: Metabolic Regulation of Transcription Through Compartmentalized NAD+ Biosynthesis


Speaker: Keun Woo Ryu, Ph.D., University of Texas Southwestern Medical Center (Host : Yong-Seok Oh)


Time: 15:00, September 12 (Wed), 2018
        

Venue: Room 114, Building E4, DGIST


Abstract : NAD+ is synthesized in distinct subcellular compartments by three different nicotinamide mononucleotide adenylyl transferases (NMNATs 1, 2, and 3).  The biological role of compartmentalized NAD+ synthesis, however, is largely unknown.  We found that compartmentalized NAD+ synthesis acts to integrate cellular glucose metabolism and the adipogenic transcription program during adipocyte differentiation.  Nuclear NAD+ is depleted by the induction of cytoplasmic NMNAT-2, whose levels rapidly increase concomitantly with glucose metabolism during differentiation.  Competition between nuclear NMNAT-1 and cytoplasmic NMNAT-2 for the common substrate, nicotinamide mononucleotide (NMN), leads to a precipitous reduction in nuclear NAD+ synthesis by NMNAT-1.  This inhibits the catalytic activity of poly(ADP-ribose) polymerase 1 (PARP-1), an NAD+-dependent nuclear enzyme that ADP-ribosylates and inhibits the adipogenic transcription factor, C/EBPβ.  Subsequent reversal of PARP-1-mediated repression and enhanced binding of C/EBPβ to adipogenic target genes drives differentiation.  Thus, compartmentalized NAD+ synthesis functions as an integrator of cellular metabolism and signal-dependent transcriptional programs.

 

Person in charge : Sora Lee


Contact: srlee@dgist.ac.kr, 053)785-6102

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